Monoclonal antibodies (mAbs) are produced from identical B lymphocytes, ensuring that they are homogenous and highly specific for their target. This specificity arises because mAbs bind to a single epitope, allowing precise targeting in various biological and therapeutic applications. Their homogeneity also provides significant advantages in research, where they are widely used to study molecular conformational changes, protein-protein interactions, and phosphorylation states.
Once a hybridoma cell line is established—created by fusing an immune B cell with a myeloma cell—the production of mAbs becomes a renewable resource. This makes them a constant and reliable tool in both research and therapeutic settings. The hybridoma process ensures that large quantities of antibodies can be produced over time without the need for repeated immunization, making mAbs a scalable solution for many applications.
In research, mAbs are valuable in identifying individual proteins in complex families. For example, in protein interaction studies, mAbs can be used to differentiate between closely related isoforms or to track post-translational modifications, such as phosphorylation, offering insights into cellular signaling pathways. These capabilities make them useful in fields like proteomics, structural biology, and molecular diagnostics.
mAbs in Therapeutic Development
Monoclonal antibody drugs are among the fastest-growing categories of FDA-approved therapies. Currently, nearly 20% of the FDA’s yearly drug approvals are mAb-based therapies, with most targeting cancers.1 These therapies are designed to exploit the unique markers present on tumor cells, such as overexpressed growth factor receptors or immune checkpoint proteins like PD-1/PD-L1.
In cancer therapy, mAbs can function in multiple ways. They can directly target and neutralize cancer cells by binding to cell surface antigens, marking them for destruction by the immune system. Some mAbs are conjugated with toxins or radioactive particles, delivering lethal agents directly to cancer cells. Others, like checkpoint inhibitors, unleash the immune system to attack cancer cells by blocking inhibitory signals that prevent immune activation.
In addition to cancer, mAbs have found success in treating autoimmune diseases, infectious diseases, and inflammatory disorders. For example, the anti-TNF mAbs used in rheumatoid arthritis neutralize pro-inflammatory cytokines, reducing the chronic inflammation that drives the disease. In infectious diseases, mAbs can be designed to neutralize pathogens or infected cells, playing a crucial role in viral and bacterial infection management.
Monoclonal Antibodies in Cancer Treatment
One of the key advantages of mAbs in cancer therapy is their ability to recognize specific tumor-associated antigens (TAAs), which are proteins or molecules present at higher levels on cancer cells compared to normal cells. By exploiting this difference, mAbs can deliver targeted treatment, reducing the risk of harming healthy tissue.
A well-known example is trastuzumab (Herceptin), a monoclonal antibody that targets the HER2 receptor, which is overexpressed in certain breast cancers. By binding to HER2, trastuzumab blocks downstream signaling pathways that promote cell growth, thereby inhibiting tumor proliferation. It also triggers immune-mediated destruction of cancer cells via mechanisms like antibody-dependent cellular cytotoxicity (ADCC).
Other mAbs, like rituximab, target the CD20 antigen on B cells and are used to treat B-cell non-Hodgkin’s lymphomas and some autoimmune diseases. This targeted action ensures that cancer cells expressing CD20 are selectively killed, while sparing most other cells, leading to improved therapeutic outcomes with fewer side effects compared to non-targeted therapies.
More recently, immune checkpoint inhibitors like nivolumab and pembrolizumab have shown success in treating multiple cancer types. These mAbs target the PD-1 receptor on T cells, preventing cancer cells from evading immune surveillance. By blocking inhibitory signals, these mAbs re-energize T cells to attack tumors, representing a paradigm shift in cancer immunotherapy.
mAbs Beyond Oncology
While mAbs are most commonly associated with cancer therapy, their use has expanded into treating autoimmune, infectious, cardiovascular, genetic, metabolic, musculoskeletal, neurological, and ophthalmological diseases.
In autoimmune diseases, where the immune system mistakenly attacks healthy tissue, mAbs can be used to block inflammatory molecules or immune checkpoints that drive the disease process. In rheumatoid arthritis (RA), for example, anti-TNF mAbs such as infliximab and adalimumab have revolutionized treatment by neutralizing tumor necrosis factor (TNF), a cytokine that plays a central role in promoting inflammation. These therapies have significantly reduced disease progression and improved the quality of life for many patients.
Monoclonal antibodies are also gaining ground in the treatment of infectious diseases. During the COVID-19 pandemic, mAbs like bamlanivimab were developed to neutralize the SARS-CoV-2 virus, preventing it from entering human cells and replicating. These antiviral antibodies are a critical tool in combating viral infections, especially for patients with weakened immune systems or those at high risk of severe disease.
Moreover, the potential for mAbs in treating bacterial infections is under investigation. Certain monoclonal antibodies are being designed to target bacterial toxins or virulence factors, providing an alternative to traditional antibiotics, particularly in cases of antibiotic resistance.
- Mullard, A. (2021). FDA approves 100th monoclonal antibody product. https://doi.org/10.1038/d41573-021-00079-7